The goal of our research is to determine the functional significance of interspecies differences in structural features of amelogenesis in order to better understand how to enhance sound enamel formation and eliminate pathology in humans. Mammalian amelogenesis is a unified process with temporal and spatial displacement of some component events of that process among various species. That is, interspecies heterogeneity observed in amelogenesis represents variations on a common theme. Amelogenesis has been segmented into three major stages; presecretory, secretory, and maturation (or resorptive), each of which is readily discernible in all mammalian tooth buds. These stages refer solely to enamel matrix proteins, but not necessarily to exclusive functions of ameloblasts or other cells of the enamel organ at any specific stage. We propose to test the hypothesis that within each of the three stages secretion and resorption occurs. In contrast to rodents, animals whose teeth form rapidly, specific events in amelogenesis of cats are very clearly defined in time and space. Consequently this is the model proposed here. Of particular importance to this study are the putative secretory and resorptive functions of ameloblasts in the presecretory stage, pharmacologically altered secretion, and the speculated resorptive functions of secretory stage ameloblasts. We will also study the role of the vasculature in resorption and the possible secretory function of ameloblasts and papillary cells in the maturation stage. We will use appropriate techniques, within our expertise, to identify cells of the enamel organ functioning in secretion and those functioning in resorption. Ultrastructural cytochemistry and short term autoradiography will be used to localize secretory cells, whereas longer term pulse chase methods will localize sites of resorption. Horseradish peroxidase and myoglobin tracer studies, in conjunction with scanning microscopy of lateral cell membranes, will also indicate sites of resorption. Both secretion and resorption sites will be further identified using colchicine, tetracycline, and fluoride to alter normal cell form and function. We will examine vascular casts of the maturation stage to determine if the vascular pattern is compatible with a counter-current mechanism for enamel mineralization and matrix protein removal.